Pharmacotherapy for Pregnant Women with Opioid Use Disorder

1 Introduction

This project focuses on Analysis 2 of the Study Protocol, which aims to characterize pregnant individuals with OUD and examine hazards of maternal death and overdose. A poster was presented at Academy Health annual research meeting focusing on analysis on those with OUD and at least one day of MOUD prescription. (Section 7)

1.1 Methods

Data Source

• TennCare data
• TN all payer hospitalization database
• Birth and death certificates
• US Census data

Inclusion Criteria

• Women 15-44 years old
• Delivery of an infant >=20 weeks between 2007-2020
• Continuous enrollment in TennCare from 90 pre-delivery through 41 days post partum
• No sickle cell disease or active malignancy
• With and without MOUD receipt initially, but only included those with MOUD for main analysis
• Up to 5-days gap of continuous enrollment

• Exposure: Days of MOUD supply between -90 days prior to delivery and +41 days post-delivery (maximum number of days = 132)
• Covariates also collected during exposure period
• Outcomes: first event of either overdose or death from 42 days post-delivery

Statistical analysis

Descriptive statistics were computed using frequencies (proportions) and medians (IQRs) as appropriate for the overall sample and also stratified by timing of MOUD receipt. Timing of MOUD receipt variable was categorized relative to timing of delivery and has two levels: receipt during one period only either pre- or post-delivery or receipt during both pre- and post-delivery periods. Due to the low number of outcomes, several variables were collapsed into one. These variables are listed below.

• Route of delivery: Cesarean or Vaginal (Vaginal + Forcep + Vacuum)
• Pain conditions: Back pain + dental pain + fibromyalgia + indicator for NSAIDs
• Alcohol use disorder + other substance use
• Benzodiazepine + Anticonvulsant use
• Anxiety + Depression

After calculating the number of days of MOUD receipt, various histograms were plotted to examine differences by method. Then, multivariable Cox Proportional hazards model were used to determine the associations between total days of MOUD receipt as the main exposure and death or overdose as the outcome. For individuals with multiple outcomes, the earliest outcome was used. Outcomes that occurred during the follow-up period were counted if they were captured in the TN all payer database if an individual lost eligibility for TennCare. Average dose per day of MOUD receipt (qty*dose)/(days supply) was also calculated and described in the table. Average days supply and dose from the pre-delivery period that exceeded 90 days was carried over and added to the post-delivery period.

The Cox model was first modeled using linear continuous terms, due to the limited degrees of freedom. However, year of delivery was determined to be non-linear and was modeled using a restricted cubic spline with 3 knots. These models included the following covariates: year of delivery, total day MOUD receipt, age at delivery, gestation weeks, route of delivery, combined pain conditions, alcohol/other substance use, benzodiazepine/anticonvulsant use, anxiety/depression, maternal morbidity (CDC defined). Additional covariates were included initially but were removed due to the small number of outcomes. These include race/ethnicity combined, number of previous pregnancies, schizophrenia/personality disorder, CDC social vulnerability index, and timing of MOUD receipt (one or two periods relative to delivery). Robust standard errors clustered at the individual level were computed.

Additonal notes: few outcomes (<5) prior to 2015

2 Only including data of women with MOUD receipt

2.1 Descriptive Statistics

• There are 9048 pregnancies in 7559 unique individuals

  	N	Overall
  		(N=9048)
  Year of delivery	9048 (100.00)
  Median (interquartile range)		2016 (2014—2018)
  Range		2007—2020
  Age at delivery	9048 (100.00)
  Median (interquartile range)		27 (24—31)
  Range		17—44
  Number of Gestation weeks	9048 (100.00)
  Median (interquartile range)		39 (37—39)
  Range		21—42
  Race	9048 (100.00)
  American Indian or Alaska Native		21/9048 (0.23)
  Asian or Pacific Islander		12/9048 (0.13)
  Black of African American		242/9048 (2.67)
  Other or Unknown		60/9048 (0.66)
  White		8713/9048 (96.30)
  Hispanic : Not Hispanic	9043 (99.94)	8964/9043 (99.13)
  Race/Ethnicity combined	9048 (100.00)
  Hispanic		79/9048 (0.87)
  Non-Hispanic Asian		11/9048 (0.12)
  Non-Hispanic Black		240/9048 (2.65)
  Non-Hispanic Other		58/9048 (0.64)
  Non-Hispanic White		8660/9048 (95.71)
  Route of delivery : Vaginal	9048 (100.00)	5876/9048 (64.94)
  Number of previous pregnancies	8886 (98.21)
  Median (interquartile range)		2 (1—3)
  Range		0—23
  Final outcome	9048 (100.00)
  Death		39/9048 (0.43)
  Overdose		109/9048 (1.20)
  Loss of enrollment		1022/9048 (11.30)
  Censored		7878/9048 (87.07)
  Final outcome (w/o all payer data)	9048 (100.00)
  Death		15/9048 (0.17)
  Overdose		103/9048 (1.14)
  Loss of enrollment		1052/9048 (11.63)
  Censored		7878/9048 (87.07)
  Total days supplied MOUD	9048 (100.00)
  Median (interquartile range)		124 (81—132)
  Range		1—132
  Total days supplied MOUD before delivery	9048 (100.00)
  Median (interquartile range)		90 (60—90)
  Range		0—90
  Total days supplied MOUD after delivery	9048 (100.00)
  Median (interquartile range)		42 (14—42)
  Range		0—42
  Total days supplied MOUD (method 2)	9048 (100.00)
  Median (interquartile range)		132 (81—132)
  Range		1—132
  Total days supplied MOUD before delivery (method 2)	9048 (100.00)
  Median (interquartile range)		90 (60—90)
  Range		0—90
  Total days supplied MOUD after delivery (method 2)	9048 (100.00)
  Median (interquartile range)		42 (36—42)
  Range		0—42
  Total days supplied MOUD (method 3)	9048 (100.00)
  Median (interquartile range)		88 (43—111)
  Range		1—132
  Total days supplied MOUD before delivery (method 3)	9048 (100.00)
  Median (interquartile range)		61 (28—77)
  Range		0—90
  Total days supplied MOUD after delivery (method 3)	9048 (100.00)
  Median (interquartile range)		29 (12—40)
  Range		0—42
  Avg dose pre-delivery (mg)	9048 (100.00)
  Median (interquartile range)		13.93 (8.00—16.00)
  Range		0.00—50.00
  Avg dose post-delivery (mg)	9048 (100.00)
  Median (interquartile range)		10.45 (4.00—16.00)
  Range		0.00—380.00
  Avg dose exposure (mg)	9048 (100.00)
  Median (interquartile range)		14.07 (9.55—16.00)
  Range		0.00—380.00
  Total days buprenorphine before delivery (method 3)	8816 (97.44)
  Median (interquartile range)		62.00 (30.00—77.00)
  Range		0.00—90.00
  Total days buprenorphine after delivery (method 3)	8816 (97.44)
  Median (interquartile range)		30.00 (12.00—40.00)
  Range		0.00—42.00
  Total days supplied buprenorphine	8816 (97.44)
  Median (interquartile range)		89.00 (45.00—112.00)
  Range		1.00—132.00
  Avg dose BUP pre-delivery (mg)	8816 (97.44)
  Median (interquartile range)		13.89 (8.00—16.00)
  Range		0.00—40.00
  Avg dose BUP post-delivery (mg)	8816 (97.44)
  Median (interquartile range)		9.87 (4.00—16.00)
  Range		0.00—42.67
  Avg dose BUP exposure (mg)	8816 (97.44)
  Median (interquartile range)		14.00 (9.18—16.00)
  Range		0.00—42.67
  Type of MOUD	9048 (100.00)
  Both		139/9048 (1.54)
  Buprenorphine only		8700/9048 (96.15)
  Naltrexone only		209/9048 (2.31)
  Combined pain : Yes	9048 (100.00)	7201/9048 (79.59)
  Schizophrenia or personality disorder : Yes	9048 (100.00)	676/9048 (7.47)
  Alcohol or other substance use : Yes	9048 (100.00)	3996/9048 (44.16)
  Benzodiazepine or anticonvulsant use : Yes	9048 (100.00)	1303/9048 (14.40)
  Maternal morbidity : Yes	9048 (100.00)	636/9048 (7.03)
  Anxiety and depression combined : Yes	9048 (100.00)	4085/9048 (45.15)
  Back pain : Yes	9048 (100.00)	3197/9048 (35.33)
  Med muscle relaxant use : Yes	9048 (100.00)	453/9048 (5.01)
  Med NSAIDS : Yes	9048 (100.00)	5737/9048 (63.41)
  Bipolar disorder : Yes	9048 (100.00)	914/9048 (10.10)
  Depression : Yes	9048 (100.00)	3489/9048 (38.56)
  Maternal morbidity : Yes	9048 (100.00)	636/9048 (7.03)
  Med benzodiazepine use : Yes	9048 (100.00)	890/9048 (9.84)
  Schizophrenia psychotic disorders : Yes	9048 (100.00)	542/9048 (5.99)
  Tobacco use : Yes	9048 (100.00)	6267/9048 (69.26)
  Dental pain : Yes	9048 (100.00)	348/9048 (3.85)
  Alcohol use disorder : Yes	9048 (100.00)	560/9048 (6.19)
  Other substance use : Yes	9048 (100.00)	3814/9048 (42.15)
  Anxiety : Yes	9048 (100.00)	1766/9048 (19.52)
  Fibromyalgia : Yes	9048 (100.00)	454/9048 (5.02)
  Med anticonvulsant use : Yes	9048 (100.00)	497/9048 (5.49)
  Personality disorder : Yes	9048 (100.00)	247/9048 (2.73)
  CDC SVI overall percentile ranking of all 4 themes	8459 (93.49)
  Median (interquartile range)		0.58 (0.37—0.78)
  Range		0.00—1.00

  N is the number of non-missing value. ¹Kruskal-Wallis. ²Pearson. ³Wilcoxon.
  
  

2.2 By cases

	N	No outcome	Had outcome	Test Statistic
		(N=8900)	(N=148)
Year of delivery	9048 (100.00)			F1,9046=41.30, P<0.00013
Median (interquartile range)		2016 (2014—2018)	2018 (2016—2019)
Range		2007—2020	2007—2020
Age at delivery	9048 (100.00)			F1,9046=0.63, P=0.42663
Median (interquartile range)		27 (24—31)	27 (25—31)
Range		17—44	19—41
Number of Gestation weeks	9048 (100.00)			F1,9046=6.82, P=0.00903
Median (interquartile range)		39 (37—39)	38 (37—39)
Range		21—42	25—42
Race	9048 (100.00)			Χ2 4=28.15, P<0.00012
American Indian or Alaska Native		20/8900 (0.22)	1/148 (0.68)
Asian or Pacific Islander		12/8900 (0.13)	0/148 (0.00)
Black of African American		237/8900 (2.66)	5/148 (3.38)
Other or Unknown		54/8900 (0.61)	6/148 (4.05)
White		8577/8900 (96.37)	136/148 (91.89)
Hispanic : Not Hispanic	9043 (99.94)	8818/8895 (99.13)	146/148 (98.65)	Χ2 1=0.40, P=0.52892
Race/Ethnicity combined	9048 (100.00)			Χ2 4=28.54, P<0.00012
Hispanic		77/8900 (0.87)	2/148 (1.35)
Non-Hispanic Asian		11/8900 (0.12)	0/148 (0.00)
Non-Hispanic Black		235/8900 (2.64)	5/148 (3.38)
Non-Hispanic Other		52/8900 (0.58)	6/148 (4.05)
Non-Hispanic White		8525/8900 (95.79)	135/148 (91.22)
Route of delivery : Vaginal	9048 (100.00)	5780/8900 (64.94)	96/148 (64.86)	Χ2 1=0.00, P=0.98412
Number of previous pregnancies	8886 (98.21)			F1,8884=1.14, P=0.28553
Median (interquartile range)		2 (1—3)	2 (1—3)
Range		0—23	0—12
Final outcome	9048 (100.00)			Χ2 3=9048.00, P<0.00012
Death		0/8900 (0.00)	39/148 (26.35)
Overdose		0/8900 (0.00)	109/148 (73.65)
Loss of enrollment		1022/8900 (11.48)	0/148 (0.00)
Censored		7878/8900 (88.52)	0/148 (0.00)
Final outcome (w/o all payer data)	9048 (100.00)			Χ2 3=7236.62, P<0.00012
Death		0/8900 (0.00)	15/148 (10.14)
Overdose		0/8900 (0.00)	103/148 (69.59)
Loss of enrollment		1022/8900 (11.48)	30/148 (20.27)
Censored		7878/8900 (88.52)	0/148 (0.00)
Total days supplied MOUD (method 3)	9048 (100.00)			F1,9046=9.23, P=0.00243
Median (interquartile range)		88 (43—111)	72 (30—106)
Range		1—132	2—131
Total days supplied MOUD before delivery (method 3)	9048 (100.00)			F1,9046=5.25, P=0.02203
Median (interquartile range)		62 (29—77)	53 (17—76)
Range		0—90	0—89
Total days supplied MOUD after delivery (method 3)	9048 (100.00)			F1,9046=9.99, P=0.00163
Median (interquartile range)		30 (12—40)	22 (6—36)
Range		0—42	0—42
Avg dose pre-delivery (mg)	9048 (100.00)			F1,9046=1.06, P=0.30233
Median (interquartile range)		13.95 (8.00—16.00)	12.62 (5.99—16.00)
Range		0.00—50.00	0.00—50.00
Avg dose post-delivery (mg)	9048 (100.00)			F1,9046=0.10, P=0.75273
Median (interquartile range)		10.47 (4.00—16.00)	10.21 (2.79—16.00)
Range		0.00—380.00	0.00—31.00
Avg dose exposure (mg)	9048 (100.00)			F1,9046=0.00, P=0.95583
Median (interquartile range)		14.07 (9.59—16.00)	13.71 (8.40—16.00)
Range		0.00—380.00	1.94—50.00
Total days buprenorphine before delivery (method 3)	8816 (97.44)			F1,8814=6.92, P=0.00853
Median (interquartile range)		62.00 (30.00—77.83)	49.00 (17.67—76.00)
Range		0.00—90.00	0.00—89.00
Total days buprenorphine after delivery (method 3)	8816 (97.44)			F1,8814=13.54, P=0.00023
Median (interquartile range)		30.00 (12.00—40.00)	22.00 (5.00—36.00)
Range		0.00—42.00	0.00—42.00
Total days supplied buprenorphine	8816 (97.44)			F1,8814=11.99, P=0.00053
Median (interquartile range)		89.00 (45.00—112.00)	71.00 (28.00—105.67)
Range		1.00—132.00	2.00—131.00
Avg dose BUP pre-delivery (mg)	8816 (97.44)			F1,8814=2.18, P=0.13973
Median (interquartile range)		13.92 (8.00—16.00)	12.44 (6.14—16.00)
Range		0.00—40.00	0.00—24.24
Avg dose BUP post-delivery (mg)	8816 (97.44)			F1,8814=0.13, P=0.72263
Median (interquartile range)		9.88 (4.00—16.00)	9.18 (0.00—16.00)
Range		0.00—42.67	0.00—31.00
Avg dose BUP exposure (mg)	8816 (97.44)			F1,8814=0.00, P=0.97663
Median (interquartile range)		14.00 (9.21—16.00)	13.36 (8.38—16.00)
Range		0.00—42.67	1.00—31.00
Combined pain : Yes	9048 (100.00)	7095/8900 (79.72)	106/148 (71.62)	Χ2 1=5.88, P=0.01542
Schizophrenia or personality disorder : Yes	9048 (100.00)	655/8900 (7.36)	21/148 (14.19)	Χ2 1=9.82, P=0.00172
Alcohol or other substance use : Yes	9048 (100.00)	3924/8900 (44.09)	72/148 (48.65)	Χ2 1=1.23, P=0.26802
Benzodiazepine or anticonvulsant use : Yes	9048 (100.00)	1275/8900 (14.33)	28/148 (18.92)	Χ2 1=2.49, P=0.11452
Maternal morbidity : Yes	9048 (100.00)	626/8900 (7.03)	10/148 (6.76)	Χ2 1=0.02, P=0.89602
Anxiety and depression combined : Yes	9048 (100.00)	3991/8900 (44.84)	94/148 (63.51)	Χ2 1=20.49, P<0.00012
Back pain : Yes	9048 (100.00)	3162/8900 (35.53)	35/148 (23.65)	Χ2 1=8.99, P=0.00272
Med muscle relaxant use : Yes	9048 (100.00)	444/8900 (4.99)	9/148 (6.08)	Χ2 1=0.37, P=0.54562
Med NSAIDS : Yes	9048 (100.00)	5650/8900 (63.48)	87/148 (58.78)	Χ2 1=1.39, P=0.23912
Bipolar disorder : Yes	9048 (100.00)	883/8900 (9.92)	31/148 (20.95)	Χ2 1=19.48, P<0.00012
Depression : Yes	9048 (100.00)	3402/8900 (38.22)	87/148 (58.78)	Χ2 1=25.97, P<0.00012
Maternal morbidity : Yes	9048 (100.00)	626/8900 (7.03)	10/148 (6.76)	Χ2 1=0.02, P=0.89602
Med benzodiazepine use : Yes	9048 (100.00)	875/8900 (9.83)	15/148 (10.14)	Χ2 1=0.02, P=0.90212
Schizophrenia psychotic disorders : Yes	9048 (100.00)	523/8900 (5.88)	19/148 (12.84)	Χ2 1=12.53, P=0.00042
Tobacco use : Yes	9048 (100.00)	6160/8900 (69.21)	107/148 (72.30)	Χ2 1=0.65, P=0.42002
Dental pain : Yes	9048 (100.00)	341/8900 (3.83)	7/148 (4.73)	Χ2 1=0.32, P=0.57302
Alcohol use disorder : Yes	9048 (100.00)	536/8900 (6.02)	24/148 (16.22)	Χ2 1=26.05, P<0.00012
Other substance use : Yes	9048 (100.00)	3744/8900 (42.07)	70/148 (47.30)	Χ2 1=1.63, P=0.20132
Anxiety : Yes	9048 (100.00)	1719/8900 (19.31)	47/148 (31.76)	Χ2 1=14.35, P=0.00022
Fibromyalgia : Yes	9048 (100.00)	447/8900 (5.02)	7/148 (4.73)	Χ2 1=0.03, P=0.87152
Med anticonvulsant use : Yes	9048 (100.00)	481/8900 (5.40)	16/148 (10.81)	Χ2 1=8.20, P=0.00422
Personality disorder : Yes	9048 (100.00)	240/8900 (2.70)	7/148 (4.73)	Χ2 1=2.27, P=0.13222
CDC SVI overall percentile ranking of all 4 themes	8459 (93.49)			F1,8457=0.69, P=0.40693
Median (interquartile range)		0.58 (0.37—0.78)	0.54 (0.33—0.81)
Range		0.00—1.00	0.00—1.00

N is the number of non-missing value. ¹Kruskal-Wallis. ²Pearson. ³Wilcoxon.

2.3 MOUD information

	N	All
		(N=9048)
MOUD pre-delivery (method 1)	9048 (100.00)
No MOUD		823/9048 (9.10)
MOUD		8225/9048 (90.90)
MOUD pre-delivery (method 2)	9048 (100.00)
No MOUD		823/9048 (9.10)
MOUD		8225/9048 (90.90)
MOUD pre-delivery (method 3)	9048 (100.00)
No MOUD		830/9048 (9.17)
MOUD		8218/9048 (90.83)
MOUD post-delivery (method 1)	9048 (100.00)
No MOUD		1902/9048 (21.02)
MOUD		7146/9048 (78.98)
MOUD post-delivery (method 2)	9048 (100.00)
No MOUD		1033/9048 (11.42)
MOUD		8015/9048 (88.58)
MOUD post-delivery (method 3)	9048 (100.00)
No MOUD		1200/9048 (13.26)
MOUD		7848/9048 (86.74)
MOUD pre and post (method 1)	9048 (100.00)
No MOUD		0/9048 (0.00)
Both pre and post		6323/9048 (69.88)
Either pre or post		2725/9048 (30.12)
MOUD pre and post (method 2)	9048 (100.00)
No MOUD		0/9048 (0.00)
Both pre and post		7192/9048 (79.49)
Either pre or post		1856/9048 (20.51)
MOUD pre and post (method 3)	9048 (100.00)
No MOUD		0/9048 (0.00)
Both pre and post		7018/9048 (77.56)
Either pre or post		2030/9048 (22.44)

N is the number of non-missing value. ¹Kruskal-Wallis. ²Pearson. ³Wilcoxon.

2.4 Characteristics based on MOUD timing (method 3)

2.4.1 Two categories

	N	Both pre and post	Either pre or post	Test Statistic
		(N=7018)	(N=2030)
Year of delivery	9048 (100.00)			F1,9046=7.23, P=0.00723
Median (interquartile range)		2016 (2014—2018)	2016 (2014—2018)
Range		2007—2020	2007—2020
Year of delivery as categorical	9048 (100.00)			Χ2 13=58.99, P<0.00012
2007		36/7018 (0.51)	15/2030 (0.74)
2008		77/7018 (1.10)	44/2030 (2.17)
2009		130/7018 (1.85)	46/2030 (2.27)
2010		211/7018 (3.01)	67/2030 (3.30)
2011		250/7018 (3.56)	73/2030 (3.60)
2012		350/7018 (4.99)	75/2030 (3.69)
2013		568/7018 (8.09)	125/2030 (6.16)
2014		765/7018 (10.90)	172/2030 (8.47)
2015		940/7018 (13.39)	233/2030 (11.48)
2016		839/7018 (11.95)	250/2030 (12.32)
2017		687/7018 (9.79)	245/2030 (12.07)
2018		694/7018 (9.89)	233/2030 (11.48)
2019		703/7018 (10.02)	234/2030 (11.53)
2020		768/7018 (10.94)	218/2030 (10.74)
Age at delivery	9048 (100.00)			F1,9046=3.93, P=0.04733
Median (interquartile range)		27 (24—31)	27 (24—30)
Range		17—44	17—44
Number of Gestation weeks	9048 (100.00)			F1,9046=11.44, P=0.00073
Median (interquartile range)		39 (37—39)	39 (37—39)
Range		21—42	23—42
Race	9048 (100.00)			Χ2 4=9.00, P=0.06102
American Indian or Alaska Native		14/7018 (0.20)	7/2030 (0.34)
Asian or Pacific Islander		10/7018 (0.14)	2/2030 (0.10)
Black of African American		172/7018 (2.45)	70/2030 (3.45)
Other or Unknown		43/7018 (0.61)	17/2030 (0.84)
White		6779/7018 (96.59)	1934/2030 (95.27)
Hispanic : Not Hispanic	9043 (99.94)	6953/7016 (99.10)	2011/2027 (99.21)	Χ2 1=0.21, P=0.64352
Race/Ethnicity combined	9048 (100.00)			Χ2 4=11.71, P=0.01962
Hispanic		63/7018 (0.90)	16/2030 (0.79)
Non-Hispanic Asian		9/7018 (0.13)	2/2030 (0.10)
Non-Hispanic Black		172/7018 (2.45)	68/2030 (3.35)
Non-Hispanic Other		37/7018 (0.53)	21/2030 (1.03)
Non-Hispanic White		6737/7018 (96.00)	1923/2030 (94.73)
Route of delivery : Vaginal	9048 (100.00)	4509/7018 (64.25)	1367/2030 (67.34)	Χ2 1=6.61, P=0.01022
Number of previous pregnancies	8886 (98.21)			F1,8884=0.13, P=0.71453
Median (interquartile range)		2 (1—3)	2 (1—3)
Range		0—23	0—23
Final outcome	9048 (100.00)			Χ2 3=23.77, P<0.00012
Death		30/7018 (0.43)	9/2030 (0.44)
Overdose		72/7018 (1.03)	37/2030 (1.82)
Loss of enrollment		745/7018 (10.62)	277/2030 (13.65)
Censored		6171/7018 (87.93)	1707/2030 (84.09)
Final outcome 3 levels	9048 (100.00)			Χ2 2=8.41, P=0.01492
Death		30/7018 (0.43)	9/2030 (0.44)
Overdose		72/7018 (1.03)	37/2030 (1.82)
Censored		6916/7018 (98.55)	1984/2030 (97.73)
Total days supplied MOUD	9048 (100.00)			F1,9046=8769.92, P<0.00013
Median (interquartile range)		132 (104—132)	42 (28—60)
Range		4—132	1—98
Total days supplied MOUD before delivery	9048 (100.00)			F1,9046=5775.74, P<0.00013
Median (interquartile range)		90 (90—90)	20 (0—60)
Range		2—90	0—90
Total days supplied MOUD after delivery	9048 (100.00)			F1,9046=2656.27, P<0.00013
Median (interquartile range)		42 (33—42)	0 (0—36)
Range		0—42	0—42
Total days supplied MOUD (method 2)	9048 (100.00)			F1,9046=8414.06, P<0.00013
Median (interquartile range)		132 (132—132)	42 (28—60)
Range		4—132	1—132
Total days supplied MOUD before delivery (method 2)	9048 (100.00)			F1,9046=5775.74, P<0.00013
Median (interquartile range)		90 (90—90)	20 (0—60)
Range		2—90	0—90
Total days supplied MOUD after delivery (method 2)	9048 (100.00)			F1,9046=4335.52, P<0.00013
Median (interquartile range)		42 (42—42)	14 (0—42)
Range		0—42	0—42
Total days supplied MOUD (method 3)	9048 (100.00)			F1,9046=6982.53, P<0.00013
Median (interquartile range)		100 (76—116)	22 (11—34)
Range		2—132	1—89
Total days supplied MOUD before delivery (method 3)	9048 (100.00)			F1,9046=4304.76, P<0.00013
Median (interquartile range)		69 (48—80)	10 (0—30)
Range		1—90	0—89
Total days supplied MOUD after delivery (method 3)	9048 (100.00)			F1,9046=5668.64, P<0.00013
Median (interquartile range)		35 (23—41)	0 (0—11)
Range		1—42	0—41
Avg dose pre-delivery (mg)	9048 (100.00)			F1,9046=1112.53, P<0.00013
Median (interquartile range)		14.92 (9.79—16.00)	6.00 (0.00—15.65)
Range		0.25—50.00	0.00—50.00
Avg dose post-delivery (mg)	9048 (100.00)			F1,9046=1037.72, P<0.00013
Median (interquartile range)		12.00 (8.00—16.00)	0.00 (0.00—13.57)
Range		0.00—380.00	0.00—380.00
Avg dose exposure (mg)	9048 (100.00)			F1,9046=4.91, P=0.02683
Median (interquartile range)		14.04 (9.88—16.00)	14.40 (8.00—16.00)
Range		0.34—56.88	0.00—380.00
Total days buprenorphine before delivery (method 3)	8816 (97.44)			F1,8814=3812.74, P<0.00013
Median (interquartile range)		69.00 (48.00—80.00)	13.00 (0.00—32.00)
Range		0.00—90.00	0.00—89.00
Total days buprenorphine after delivery (method 3)	8816 (97.44)			F1,8814=5226.26, P<0.00013
Median (interquartile range)		35.00 (23.00—41.00)	0.00 (0.00—9.00)
Range		0.00—42.00	0.00—41.00
Total days supplied buprenorphine	8816 (97.44)			F1,8814=6204.54, P<0.00013
Median (interquartile range)		100.00 (76.00—116.00)	22.00 (11.00—35.00)
Range		2.00—132.00	1.00—89.00
Avg dose BUP pre-delivery (mg)	8816 (97.44)			F1,8814=981.32, P<0.00013
Median (interquartile range)		14.79 (9.54—16.00)	7.60 (0.00—15.65)
Range		0.00—40.00	0.00—32.00
Avg dose BUP post-delivery (mg)	8816 (97.44)			F1,8814=1152.98, P<0.00013
Median (interquartile range)		12.00 (8.00—16.00)	0.00 (0.00—11.70)
Range		0.00—33.24	0.00—42.67
Avg dose BUP exposure (mg)	8816 (97.44)			F1,8814=0.74, P=0.38903
Median (interquartile range)		13.96 (9.75—16.00)	14.41 (8.00—16.00)
Range		0.25—34.47	0.00—42.67
Combined pain : Yes	9048 (100.00)	5607/7018 (79.89)	1594/2030 (78.52)	Χ2 1=1.83, P=0.17672
Schizophrenia or personality disorder : Yes	9048 (100.00)	495/7018 (7.05)	181/2030 (8.92)	Χ2 1=7.90, P=0.00492
Alcohol or other substance use : Yes	9048 (100.00)	3069/7018 (43.73)	927/2030 (45.67)	Χ2 1=2.39, P=0.12212
Benzodiazepine or anticonvulsant use : Yes	9048 (100.00)	1031/7018 (14.69)	272/2030 (13.40)	Χ2 1=2.13, P=0.14432
Maternal morbidity : Yes	9048 (100.00)	489/7018 (6.97)	147/2030 (7.24)	Χ2 1=0.18, P=0.67112
Anxiety and depression combined : Yes	9048 (100.00)	3166/7018 (45.11)	919/2030 (45.27)	Χ2 1=0.02, P=0.89952
Back pain : Yes	9048 (100.00)	2511/7018 (35.78)	686/2030 (33.79)	Χ2 1=2.72, P=0.09922
Med muscle relaxant use : Yes	9048 (100.00)	316/7018 (4.50)	137/2030 (6.75)	Χ2 1=16.70, P<0.00012
Med NSAIDS : Yes	9048 (100.00)	4463/7018 (63.59)	1274/2030 (62.76)	Χ2 1=0.47, P=0.49152
Bipolar disorder : Yes	9048 (100.00)	711/7018 (10.13)	203/2030 (10.00)	Χ2 1=0.03, P=0.86302
Depression : Yes	9048 (100.00)	2694/7018 (38.39)	795/2030 (39.16)	Χ2 1=0.40, P=0.52722
Maternal morbidity : Yes	9048 (100.00)	489/7018 (6.97)	147/2030 (7.24)	Χ2 1=0.18, P=0.67112
Med benzodiazepine use : Yes	9048 (100.00)	695/7018 (9.90)	195/2030 (9.61)	Χ2 1=0.16, P=0.69212
Schizophrenia psychotic disorders : Yes	9048 (100.00)	400/7018 (5.70)	142/2030 (7.00)	Χ2 1=4.69, P=0.03032
Tobacco use : Yes	9048 (100.00)	4862/7018 (69.28)	1405/2030 (69.21)	Χ2 1=0.00, P=0.95392
Dental pain : Yes	9048 (100.00)	255/7018 (3.63)	93/2030 (4.58)	Χ2 1=3.82, P=0.05052
Alcohol use disorder : Yes	9048 (100.00)	416/7018 (5.93)	144/2030 (7.09)	Χ2 1=3.69, P=0.05482
Other substance use : Yes	9048 (100.00)	2916/7018 (41.55)	898/2030 (44.24)	Χ2 1=4.66, P=0.03092
Anxiety : Yes	9048 (100.00)	1363/7018 (19.42)	403/2030 (19.85)	Χ2 1=0.19, P=0.66632
Fibromyalgia : Yes	9048 (100.00)	349/7018 (4.97)	105/2030 (5.17)	Χ2 1=0.13, P=0.71692
Med anticonvulsant use : Yes	9048 (100.00)	403/7018 (5.74)	94/2030 (4.63)	Χ2 1=3.75, P=0.05282
Personality disorder : Yes	9048 (100.00)	174/7018 (2.48)	73/2030 (3.60)	Χ2 1=7.39, P=0.00652
CDC SVI overall percentile ranking of all 4 themes	8459 (93.49)			F1,8457=3.13, P=0.07673
Median (interquartile range)		0.57 (0.37—0.78)	0.59 (0.38—0.79)
Range		0.00—1.00	0.00—1.00

N is the number of non-missing value. ¹Kruskal-Wallis. ²Pearson. ³Wilcoxon.

2.4.2 Three categories

	N	Only pre	Only post	Both pre and post	Test Statistic
		(N=1200)	(N=830)	(N=7018)
Year of delivery	9048 (100.00)				F2,9045=10.35, P<0.00011
Median (interquartile range)		2016 (2014—2018)	2016 (2013—2019)	2016 (2014—2018)
Range		2007—2020	2007—2020	2007—2020
Year of delivery as categorical	9048 (100.00)				Χ2 26=217.18, P<0.00012
2007		3/1200 (0.25)	12/830 (1.45)	36/7018 (0.51)
2008		10/1200 (0.83)	34/830 (4.10)	77/7018 (1.10)
2009		16/1200 (1.33)	30/830 (3.61)	130/7018 (1.85)
2010		19/1200 (1.58)	48/830 (5.78)	211/7018 (3.01)
2011		38/1200 (3.17)	35/830 (4.22)	250/7018 (3.56)
2012		46/1200 (3.83)	29/830 (3.49)	350/7018 (4.99)
2013		67/1200 (5.58)	58/830 (6.99)	568/7018 (8.09)
2014		103/1200 (8.58)	69/830 (8.31)	765/7018 (10.90)
2015		154/1200 (12.83)	79/830 (9.52)	940/7018 (13.39)
2016		179/1200 (14.92)	71/830 (8.55)	839/7018 (11.95)
2017		160/1200 (13.33)	85/830 (10.24)	687/7018 (9.79)
2018		172/1200 (14.33)	61/830 (7.35)	694/7018 (9.89)
2019		130/1200 (10.83)	104/830 (12.53)	703/7018 (10.02)
2020		103/1200 (8.58)	115/830 (13.86)	768/7018 (10.94)
Age at delivery	9048 (100.00)				F2,9045=2.32, P=0.09791
Median (interquartile range)		27 (24—30)	27 (24—31)	27 (24—31)
Range		17—43	17—44	17—44
Number of Gestation weeks	9048 (100.00)				F2,9045=8.79, P=0.00021
Median (interquartile range)		39 (37—39)	38 (37—39)	39 (37—39)
Range		24—42	23—42	21—42
Race	9048 (100.00)				Χ2 8=10.46, P=0.23392
American Indian or Alaska Native		4/1200 (0.33)	3/830 (0.36)	14/7018 (0.20)
Asian or Pacific Islander		1/1200 (0.08)	1/830 (0.12)	10/7018 (0.14)
Black of African American		43/1200 (3.58)	27/830 (3.25)	172/7018 (2.45)
Other or Unknown		12/1200 (1.00)	5/830 (0.60)	43/7018 (0.61)
White		1140/1200 (95.00)	794/830 (95.66)	6779/7018 (96.59)
Hispanic : Not Hispanic	9043 (99.94)	1188/1198 (99.17)	823/829 (99.28)	6953/7016 (99.10)	Χ2 2=0.28, P=0.86772
Race/Ethnicity combined	9048 (100.00)				Χ2 8=12.92, P=0.11482
Hispanic		10/1200 (0.83)	6/830 (0.72)	63/7018 (0.90)
Non-Hispanic Asian		1/1200 (0.08)	1/830 (0.12)	9/7018 (0.13)
Non-Hispanic Black		42/1200 (3.50)	26/830 (3.13)	172/7018 (2.45)
Non-Hispanic Other		14/1200 (1.17)	7/830 (0.84)	37/7018 (0.53)
Non-Hispanic White		1133/1200 (94.42)	790/830 (95.18)	6737/7018 (96.00)
Route of delivery : Vaginal	9048 (100.00)	817/1200 (68.08)	550/830 (66.27)	4509/7018 (64.25)	Χ2 2=7.32, P=0.02572
Number of previous pregnancies	8886 (98.21)				F2,8883=0.09, P=0.91211
Median (interquartile range)		2 (1—3)	2 (1—3)	2 (1—3)
Range		0—19	0—23	0—23
Final outcome	9048 (100.00)				Χ2 6=31.07, P<0.00012
Death		3/1200 (0.25)	6/830 (0.72)	30/7018 (0.43)
Overdose		20/1200 (1.67)	17/830 (2.05)	72/7018 (1.03)
Loss of enrollment		150/1200 (12.50)	127/830 (15.30)	745/7018 (10.62)
Censored		1027/1200 (85.58)	680/830 (81.93)	6171/7018 (87.93)
Final outcome 3 levels	9048 (100.00)				Χ2 4=11.59, P=0.02072
Death		3/1200 (0.25)	6/830 (0.72)	30/7018 (0.43)
Overdose		20/1200 (1.67)	17/830 (2.05)	72/7018 (1.03)
Censored		1177/1200 (98.08)	807/830 (97.23)	6916/7018 (98.55)
Total days supplied MOUD	9048 (100.00)				F2,9045=4479.01, P<0.00011
Median (interquartile range)		60 (28—90)	42 (28—42)	132 (104—132)
Range		2—90	1—98	4—132
Total days supplied MOUD before delivery	9048 (100.00)				F2,9045=3895.76, P<0.00011
Median (interquartile range)		60 (28—90)	0 (0—0)	90 (90—90)
Range		2—90	0—56	2—90
Total days supplied MOUD after delivery	9048 (100.00)				F2,9045=2717.41, P<0.00011
Median (interquartile range)		0 (0—0)	42 (28—42)	42 (33—42)
Range		0—0	1—42	0—42
Total days supplied MOUD (method 2)	9048 (100.00)				F2,9045=4453.24, P<0.00011
Median (interquartile range)		60 (28—99)	42 (28—42)	132 (132—132)
Range		2—132	1—98	4—132
Total days supplied MOUD before delivery (method 2)	9048 (100.00)				F2,9045=3895.76, P<0.00011
Median (interquartile range)		60 (28—90)	0 (0—0)	90 (90—90)
Range		2—90	0—56	2—90
Total days supplied MOUD after delivery (method 2)	9048 (100.00)				F2,9045=3276.43, P<0.00011
Median (interquartile range)		0 (0—9)	42 (28—42)	42 (42—42)
Range		0—42	1—42	0—42
Total days supplied MOUD (method 3)	9048 (100.00)				F2,9045=3571.31, P<0.00011
Median (interquartile range)		30 (14—47)	14 (7—24)	100 (76—116)
Range		1—89	1—41	2—132
Total days supplied MOUD before delivery (method 3)	9048 (100.00)				F2,9045=2589.45, P<0.00011
Median (interquartile range)		30 (14—47)	0 (0—0)	69 (48—80)
Range		1—89	0—0	1—90
Total days supplied MOUD after delivery (method 3)	9048 (100.00)				F2,9045=3359.62, P<0.00011
Median (interquartile range)		0 (0—0)	14 (7—24)	35 (23—41)
Range		0—0	1—41	1—42
Avg dose pre-delivery (mg)	9048 (100.00)				F2,9045=1574.23, P<0.00011
Median (interquartile range)		14.00 (8.00—16.00)	0.00 (0.00—0.00)	14.92 (9.79—16.00)
Range		0.00—50.00	0.00—0.00	0.25—50.00
Avg dose post-delivery (mg)	9048 (100.00)				F2,9045=1993.04, P<0.00011
Median (interquartile range)		0.00 (0.00—0.00)	15.32 (9.33—16.00)	12.00 (8.00—16.00)
Range		0.00—0.00	0.00—380.00	0.00—380.00
Avg dose exposure (mg)	9048 (100.00)				F2,9045=15.65, P<0.00011
Median (interquartile range)		14.00 (8.00—16.00)	15.32 (9.33—16.00)	14.04 (9.88—16.00)
Range		0.00—50.00	0.00—380.00	0.34—56.88
Total days buprenorphine before delivery (method 3)	8816 (97.44)				F2,8813=2259.60, P<0.00011
Median (interquartile range)		30.00 (14.00—47.00)	0.00 (0.00—0.00)	69.00 (48.00—80.00)
Range		1.00—89.00	0.00—0.00	0.00—90.00
Total days buprenorphine after delivery (method 3)	8816 (97.44)				F2,8813=3058.36, P<0.00011
Median (interquartile range)		0.00 (0.00—0.00)	14.00 (7.00—24.83)	35.00 (23.00—41.00)
Range		0.00—0.00	1.00—41.00	0.00—42.00
Total days supplied buprenorphine	8816 (97.44)				F2,8813=3162.34, P<0.00011
Median (interquartile range)		30.00 (14.00—47.00)	14.00 (7.00—24.83)	100.00 (76.00—116.00)
Range		1.00—89.00	1.00—41.00	2.00—132.00
Avg dose BUP pre-delivery (mg)	8816 (97.44)				F2,8813=1327.50, P<0.00011
Median (interquartile range)		13.45 (8.00—16.00)	0.00 (0.00—0.00)	14.79 (9.54—16.00)
Range		0.00—32.00	0.00—0.00	0.00—40.00
Avg dose BUP post-delivery (mg)	8816 (97.44)				F2,8813=1877.30, P<0.00011
Median (interquartile range)		0.00 (0.00—0.00)	16.00 (8.40—16.00)	12.00 (8.00—16.00)
Range		0.00—0.00	0.00—42.67	0.00—33.24
Avg dose BUP exposure (mg)	8816 (97.44)				F2,8813=15.89, P<0.00011
Median (interquartile range)		13.45 (8.00—16.00)	16.00 (8.40—16.00)	13.96 (9.75—16.00)
Range		0.00—32.00	0.00—42.67	0.25—34.47
Combined pain : Yes	9048 (100.00)	947/1200 (78.92)	647/830 (77.95)	5607/7018 (79.89)	Χ2 2=2.11, P=0.34882
Schizophrenia or personality disorder : Yes	9048 (100.00)	98/1200 (8.17)	83/830 (10.00)	495/7018 (7.05)	Χ2 2=10.29, P=0.00582
Alcohol or other substance use : Yes	9048 (100.00)	547/1200 (45.58)	380/830 (45.78)	3069/7018 (43.73)	Χ2 2=2.40, P=0.30152
Benzodiazepine or anticonvulsant use : Yes	9048 (100.00)	160/1200 (13.33)	112/830 (13.49)	1031/7018 (14.69)	Χ2 2=2.14, P=0.34272
Maternal morbidity : Yes	9048 (100.00)	87/1200 (7.25)	60/830 (7.23)	489/7018 (6.97)	Χ2 2=0.18, P=0.91362
Anxiety and depression combined : Yes	9048 (100.00)	509/1200 (42.42)	410/830 (49.40)	3166/7018 (45.11)	Χ2 2=9.67, P=0.00792
Back pain : Yes	9048 (100.00)	415/1200 (34.58)	271/830 (32.65)	2511/7018 (35.78)	Χ2 2=3.52, P=0.17202
Med muscle relaxant use : Yes	9048 (100.00)	71/1200 (5.92)	66/830 (7.95)	316/7018 (4.50)	Χ2 2=20.97, P<0.00012
Med NSAIDS : Yes	9048 (100.00)	750/1200 (62.50)	524/830 (63.13)	4463/7018 (63.59)	Χ2 2=0.56, P=0.75662
Bipolar disorder : Yes	9048 (100.00)	132/1200 (11.00)	71/830 (8.55)	711/7018 (10.13)	Χ2 2=3.26, P=0.19582
Depression : Yes	9048 (100.00)	430/1200 (35.83)	365/830 (43.98)	2694/7018 (38.39)	Χ2 2=14.13, P=0.00092
Maternal morbidity : Yes	9048 (100.00)	87/1200 (7.25)	60/830 (7.23)	489/7018 (6.97)	Χ2 2=0.18, P=0.91362
Med benzodiazepine use : Yes	9048 (100.00)	117/1200 (9.75)	78/830 (9.40)	695/7018 (9.90)	Χ2 2=0.23, P=0.89342
Schizophrenia psychotic disorders : Yes	9048 (100.00)	78/1200 (6.50)	64/830 (7.71)	400/7018 (5.70)	Χ2 2=5.97, P=0.05062
Tobacco use : Yes	9048 (100.00)	862/1200 (71.83)	543/830 (65.42)	4862/7018 (69.28)	Χ2 2=9.48, P=0.00872
Dental pain : Yes	9048 (100.00)	55/1200 (4.58)	38/830 (4.58)	255/7018 (3.63)	Χ2 2=3.82, P=0.14782
Alcohol use disorder : Yes	9048 (100.00)	74/1200 (6.17)	70/830 (8.43)	416/7018 (5.93)	Χ2 2=8.03, P=0.01802
Other substance use : Yes	9048 (100.00)	535/1200 (44.58)	363/830 (43.73)	2916/7018 (41.55)	Χ2 2=4.80, P=0.09052
Anxiety : Yes	9048 (100.00)	245/1200 (20.42)	158/830 (19.04)	1363/7018 (19.42)	Χ2 2=0.78, P=0.67662
Fibromyalgia : Yes	9048 (100.00)	63/1200 (5.25)	42/830 (5.06)	349/7018 (4.97)	Χ2 2=0.17, P=0.91922
Med anticonvulsant use : Yes	9048 (100.00)	55/1200 (4.58)	39/830 (4.70)	403/7018 (5.74)	Χ2 2=3.76, P=0.15242
Personality disorder : Yes	9048 (100.00)	38/1200 (3.17)	35/830 (4.22)	174/7018 (2.48)	Χ2 2=9.43, P=0.00892
CDC SVI overall percentile ranking of all 4 themes	8459 (93.49)				F2,8456=5.74, P=0.00321
Median (interquartile range)		0.62 (0.40—0.81)	0.57 (0.36—0.75)	0.57 (0.37—0.78)
Range		0.00—1.00	0.00—1.00	0.00—1.00

N is the number of non-missing value. ¹Kruskal-Wallis. ²Pearson. ³Wilcoxon.

2.5 Histogram of MOUD days supplied

2.5.1 Before delivery up to 90 days (Method 1)

2.5.2 Before delivery up to 90 days (Method 2)

2.5.3 Before delivery up to 90 days (Method 3)

2.5.4 After delivery up to 41 days (Method 1)

2.5.5 After delivery up to 41 days (Method 3)

2.5.6 After delivery up to 41 days (Method 3)

2.5.7 Entire exposure (Method 1)

2.5.8 Entire exposure (Method 2)

2.5.9 Entire exposure (Method 3)

Survival Analysis

2.6 Kaplan Meier Plot

Call: survfit(formula = Surv(days.to.event, outcome.bin) ~ 1, data = moud)

        n events median 0.95LCL 0.95UCL
[1,] 9048    148     NA      NA      NA

   Min. 1st Qu.  Median    Mean 3rd Qu.    Max. 
    2.0    92.5   184.5   176.2   258.8   323.0 

time	probability
2	0.9998895
7	0.9997790
8	0.9995579
10	0.9994474
17	0.9993369
18	0.9992263
19	0.9991158
27	0.9990053
32	0.9988948
34	0.9987843
35	0.9985632
38	0.9984527
41	0.9983422
42	0.9982317
43	0.9981211
45	0.9979001
47	0.9977896
52	0.9975685
59	0.9973475
60	0.9972370
61	0.9971264
63	0.9970159
65	0.9969054
66	0.9967949
69	0.9966844
70	0.9965738
72	0.9964633
75	0.9963528
77	0.9962423
87	0.9961317
91	0.9960212
93	0.9959107
95	0.9958002
97	0.9956897
101	0.9954686
110	0.9953581
111	0.9952476
112	0.9951370
118	0.9949160
120	0.9948055
121	0.9946950
125	0.9945844
128	0.9944739
131	0.9943634
138	0.9941424
140	0.9940318
144	0.9939213
147	0.9938108
151	0.9935897
153	0.9934792
156	0.9932582
166	0.9931477
169	0.9930371
171	0.9929266
173	0.9928161
175	0.9927056
177	0.9925950
178	0.9924845
180	0.9923740
181	0.9922635
182	0.9921530
184	0.9920424
185	0.9919319
188	0.9917109
193	0.9916004
199	0.9914898
204	0.9913793
208	0.9912688
211	0.9911583
213	0.9909372
214	0.9908267
215	0.9906057
216	0.9904951
217	0.9902741
220	0.9901636
222	0.9900531
223	0.9899425
228	0.9897215
229	0.9896110
233	0.9895004
235	0.9893899
236	0.9892794
239	0.9891689
240	0.9889478
242	0.9888373
244	0.9887268
245	0.9886163
246	0.9883952
247	0.9882847
250	0.9881742
253	0.9880637
254	0.9879531
258	0.9878426
261	0.9876216
262	0.9875111
263	0.9874005
265	0.9872900
267	0.9871795
268	0.9870690
270	0.9868479
271	0.9867374
272	0.9866269
274	0.9864058
275	0.9862953
279	0.9861848
281	0.9860743
287	0.9858532
289	0.9857427
290	0.9856322
295	0.9854111
296	0.9853006
298	0.9850796
300	0.9849691
301	0.9848585
302	0.9847480
304	0.9846375
305	0.9845270
308	0.9843059
310	0.9840849
313	0.9839744
316	0.9838638
319	0.9837533
321	0.9836428
323	0.9836428

2.7 Time to event for overdose and death

deathod$days.to.event

n	missing	distinct	Info	Mean	pMedian	Gmd	.05	.10	.25	.50	.75	.90	.95
148	0	123	1	177.3	177.5	108.5	21.8	41.7	94.5	188.0	261.0	296.6	307.0

lowest : 2 7 8 10 17 , highest: 310 313 316 319 321 death$days.to.event

n	missing	distinct	Info	Mean	pMedian	Gmd	.05	.10	.25	.50	.75	.90	.95
39	0	38	1	156.7	156.5	112.7	18.8	34.4	60.0	171.0	243.5	279.4	290.5

lowest : 2 17 19 32 35 , highest: 279 281 290 295 308 od$days.to.event

n	missing	distinct	Info	Mean	pMedian	Gmd	.05	.10	.25	.50	.75	.90	.95
109	0	98	1	184.7	185.5	106.5	29.8	44.6	111.0	208.0	262.0	300.2	309.2

lowest : 7 8 10 18 27 , highest: 310 313 316 319 321

3 Multivariable Cox PH model

3.1 Linear continuous terms

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Year of delivery	2016	2018	2	0.34850	0.08003	0.191600	0.50540
Hazard Ratio	2016	2018	2	1.41700		1.211000	1.65800
Total days supplied MOUD (method 3)	1	31	30	-0.16070	0.06072	-0.279700	-0.04172
Hazard Ratio	1	31	30	0.85150		0.756000	0.95910
Age at delivery	27	31	4	-0.05909	0.07189	-0.200000	0.08181
Hazard Ratio	27	31	4	0.94260		0.818700	1.08500
Number of Gestation weeks	39	37	-2	0.12530	0.06235	0.003128	0.24750
Hazard Ratio	39	37	-2	1.13400		1.003000	1.28100
Route of delivery --- Cesarean:Vaginal	2	1		-0.01527	0.17740	-0.362900	0.33240
Hazard Ratio	2	1		0.98480		0.695600	1.39400
Combined pain --- Yes:No	1	2		-0.26220	0.18590	-0.626600	0.10230
Hazard Ratio	1	2		0.76940		0.534400	1.10800
Alcohol or other substance use --- Yes:No	1	2		0.18920	0.17040	-0.144800	0.52330
Hazard Ratio	1	2		1.20800		0.865200	1.68800
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.29500	0.21210	-0.120700	0.71070
Hazard Ratio	1	2		1.34300		0.886300	2.03500
Anxiety and depression combined --- Yes:No	1	2		0.53420	0.18040	0.180700	0.88770
Hazard Ratio	1	2		1.70600		1.198000	2.43000
Maternal morbidity --- Yes:No	1	2		-0.03872	0.35230	-0.729200	0.65180
Hazard Ratio	1	2		0.96200		0.482300	1.91900

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
Year of delivery	18.93	1	<0.0001
Total days supplied MOUD (method 3)	7.01	1	0.0081
Age at delivery	0.68	1	0.4107
Route of delivery	0.01	1	0.9314
Number of Gestation weeks	4.05	1	0.0443
Combined pain	1.99	1	0.1585
Alcohol or other substance use	1.23	1	0.2668
Benzodiazepine or anticonvulsant use	1.94	1	0.1639
Anxiety and depression combined	8.76	1	0.0031
Maternal morbidity	0.01	1	0.9124
TOTAL	65.24	10	<0.0001

3.1.1 Univariable HR

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Total days supplied MOUD (method 3)	1	31	30	-0.1901	0.06122	-0.3101	-0.07009
Hazard Ratio	1	31	30	0.8269		0.7334	0.93230

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
Total days supplied MOUD (method 3)	9.63	1	0.0019
TOTAL	9.63	1	0.0019

3.2 With splines

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Year of delivery	2016	2018	2	0.42100	0.09150	0.2417000	0.60040
Hazard Ratio	2016	2018	2	1.52400		1.2730000	1.82300
Total days supplied MOUD (method 3)	1	31	30	-0.16190	0.06017	-0.2798000	-0.04399
Hazard Ratio	1	31	30	0.85050		0.7559000	0.95700
Age at delivery	27	31	4	-0.06195	0.07171	-0.2025000	0.07860
Hazard Ratio	27	31	4	0.93990		0.8167000	1.08200
Number of Gestation weeks	39	37	-2	0.12370	0.06282	0.0005376	0.24680
Hazard Ratio	39	37	-2	1.13200		1.0010000	1.28000
Route of delivery --- Cesarean:Vaginal	2	1		-0.01485	0.17730	-0.3624000	0.33270
Hazard Ratio	2	1		0.98530		0.6960000	1.39500
Combined pain --- Yes:No	1	2		-0.27250	0.18690	-0.6389000	0.09388
Hazard Ratio	1	2		0.76150		0.5279000	1.09800
Alcohol or other substance use --- Yes:No	1	2		0.19770	0.17150	-0.1384000	0.53380
Hazard Ratio	1	2		1.21900		0.8707000	1.70500
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.31260	0.21520	-0.1091000	0.73430
Hazard Ratio	1	2		1.36700		0.8966000	2.08400
Anxiety and depression combined --- Yes:No	1	2		0.53080	0.18050	0.1770000	0.88460
Hazard Ratio	1	2		1.70000		1.1940000	2.42200
Maternal morbidity --- Yes:No	1	2		-0.04133	0.35150	-0.7302000	0.64750
Hazard Ratio	1	2		0.95950		0.4818000	1.91100

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
Year of delivery	26.47	2	<0.0001
Nonlinear	1.44	1	0.2308
Total days supplied MOUD (method 3)	7.24	1	0.0071
Age at delivery	0.75	1	0.3872
Route of delivery	0.01	1	0.9333
Number of Gestation weeks	3.88	1	0.0488
Combined pain	2.13	1	0.1449
Alcohol or other substance use	1.33	1	0.2489
Benzodiazepine or anticonvulsant use	2.11	1	0.1459
Anxiety and depression combined	8.64	1	0.0033
Maternal morbidity	0.01	1	0.9063
TOTAL	75.63	11	<0.0001

3.3 Linear model (only buprenorphine)

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Year of delivery	2016	2018	2	0.36370	0.08187	0.20320	0.52410
Hazard Ratio	2016	2018	2	1.43900		1.22500	1.68900
Total days supplied buprenorphine	1	31	30	-0.19710	0.06216	-0.31890	-0.07527
Hazard Ratio	1	31	30	0.82110		0.72690	0.92750
Age at delivery	27	31	4	-0.05378	0.07267	-0.19620	0.08865
Hazard Ratio	27	31	4	0.94760		0.82180	1.09300
Number of Gestation weeks	39	37	-2	0.13170	0.06160	0.01096	0.25240
Hazard Ratio	39	37	-2	1.14100		1.01100	1.28700
Route of delivery --- Cesarean:Vaginal	2	1		-0.07969	0.18050	-0.43340	0.27400
Hazard Ratio	2	1		0.92340		0.64830	1.31500
Combined pain --- Yes:No	1	2		-0.26570	0.18690	-0.63200	0.10060
Hazard Ratio	1	2		0.76670		0.53150	1.10600
Alcohol or other substance use --- Yes:No	1	2		0.25720	0.17210	-0.08015	0.59460
Hazard Ratio	1	2		1.29300		0.92300	1.81200
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.30620	0.21270	-0.11070	0.72310
Hazard Ratio	1	2		1.35800		0.89520	2.06100
Anxiety and depression combined --- Yes:No	1	2		0.53630	0.18100	0.18160	0.89110
Hazard Ratio	1	2		1.71000		1.19900	2.43800
Maternal morbidity --- Yes:No	1	2		-0.03741	0.35310	-0.72950	0.65470
Hazard Ratio	1	2		0.96330		0.48220	1.92400

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
Year of delivery	19.70	1	<0.0001
Total days supplied buprenorphine	10.05	1	0.0015
Age at delivery	0.55	1	0.4589
Route of delivery	0.19	1	0.6590
Number of Gestation weeks	4.58	1	0.0324
Combined pain	2.02	1	0.1552
Alcohol or other substance use	2.23	1	0.1349
Benzodiazepine or anticonvulsant use	2.08	1	0.1497
Anxiety and depression combined	8.77	1	0.0031
Maternal morbidity	0.01	1	0.9155
TOTAL	69.36	10	<0.0001

3.3.1 Univariate

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Total days supplied buprenorphine	1	31	30	-0.2258	0.06285	-0.3490	-0.1026
Hazard Ratio	1	31	30	0.7979		0.7054	0.9025

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
Total days supplied buprenorphine	12.90	1	0.0003
TOTAL	12.90	1	0.0003

By MOUD timing

4 Survival analysis

4.1 KM Curves

time	probability
2	0.9991667
8	0.9983333
19	0.9975000
32	0.9966667
45	0.9958333
70	0.9950000
97	0.9941667
101	0.9933333
111	0.9925000
125	0.9916667
131	0.9908333
173	0.9900000
177	0.9891667
217	0.9883333
222	0.9875000
240	0.9866667
244	0.9858333
258	0.9850000
261	0.9841667
270	0.9833333
274	0.9825000
287	0.9816667
310	0.9808333
323	0.9808333
27	0.9987952
35	0.9975904
77	0.9963855
87	0.9951807
91	0.9939759
101	0.9927711
118	0.9915663
138	0.9903614
147	0.9891566
166	0.9879518
193	0.9867470
213	0.9855422
215	0.9843373
217	0.9831325
245	0.9819277
270	0.9807229
272	0.9795181
281	0.9783133
295	0.9759036
300	0.9746988
301	0.9734940
319	0.9722892
323	0.9722892
7	0.9998575
8	0.9997150
10	0.9995725
17	0.9994300
18	0.9992875
34	0.9991451
35	0.9990026
38	0.9988601
41	0.9987176
42	0.9985751
43	0.9984326
45	0.9982901
47	0.9981476
52	0.9978626
59	0.9975777
60	0.9974352
61	0.9972927
63	0.9971502
65	0.9970077
66	0.9968652
69	0.9967227
72	0.9965802
75	0.9964377
93	0.9962952
95	0.9961528
110	0.9960103
112	0.9958678
118	0.9957253
120	0.9955828
121	0.9954403
128	0.9952978
138	0.9951553
140	0.9950128
144	0.9948703
151	0.9945854
153	0.9944429
156	0.9941579
169	0.9940154
171	0.9938729
175	0.9937304
178	0.9935879
180	0.9934454
181	0.9933029
182	0.9931604
184	0.9930180
185	0.9928755
188	0.9925905
199	0.9924480
204	0.9923055
208	0.9921630
211	0.9920205
213	0.9918780
214	0.9917355
215	0.9915930
216	0.9914506
220	0.9913081
223	0.9911656
228	0.9908806
229	0.9907381
233	0.9905956
235	0.9904531
236	0.9903106
239	0.9901681
240	0.9900256
242	0.9898832
246	0.9895982
247	0.9894557
250	0.9893132
253	0.9891707
254	0.9890282
261	0.9888857
262	0.9887432
263	0.9886007
265	0.9884583
267	0.9883158
268	0.9881733
271	0.9880308
274	0.9878883
275	0.9877458
279	0.9876033
287	0.9874608
289	0.9873183
290	0.9871758
296	0.9870333
298	0.9867484
302	0.9866059
304	0.9864634
305	0.9863209
308	0.9860359
310	0.9858934
313	0.9857509
316	0.9856084
321	0.9854659
323	0.9854659

4.2 Log-Rank Test

Call:
survdiff(formula = Surv(days.to.event, outcome.bin) ~ moud.both3div, 
    data = moud)

                                   N Observed Expected (O-E)^2/E (O-E)^2/V
moud.both3div=Only pre          1200       23     19.6     0.597     0.688
moud.both3div=Only post          830       23     13.5     6.654     7.324
moud.both3div=Both pre and post 7018      102    114.9     1.449     6.478

 Chisq= 8.7  on 2 degrees of freedom, p= 0.01 

4.3 Multivariable Cox PH model

Linear continuous terms (timing + days)

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Total days supplied MOUD (method 3)	1	31	30	-0.124800	0.09117	-0.303500	0.05387
Hazard Ratio	1	31	30	0.882700		0.738200	1.05500
Year of delivery	2016	2018	2	0.348900	0.07889	0.194300	0.50350
Hazard Ratio	2016	2018	2	1.418000		1.214000	1.65500
Age at delivery	27	31	4	-0.061480	0.07178	-0.202200	0.07921
Hazard Ratio	27	31	4	0.940400		0.816900	1.08200
Number of Gestation weeks	39	37	-2	0.119800	0.06176	-0.001211	0.24090
Hazard Ratio	39	37	-2	1.127000		0.998800	1.27200
MOUD receipt timing --- Only pre:Both pre and post	3	1		-0.004661	0.30270	-0.597900	0.58850
Hazard Ratio	3	1		0.995300		0.550000	1.80100
MOUD receipt timing --- Only post:Both pre and post	3	2		0.271700	0.31820	-0.352000	0.89540
Hazard Ratio	3	2		1.312000		0.703300	2.44800
Route of delivery --- Cesarean:Vaginal	2	1		-0.016230	0.17750	-0.364200	0.33170
Hazard Ratio	2	1		0.983900		0.694800	1.39300
Combined pain --- No:Yes	2	1		0.257400	0.18600	-0.107300	0.62200
Hazard Ratio	2	1		1.294000		0.898300	1.86300
Alcohol or other substance use --- Yes:No	1	2		0.195100	0.17040	-0.138900	0.52900
Hazard Ratio	1	2		1.215000		0.870300	1.69700
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.297500	0.21190	-0.117900	0.71290
Hazard Ratio	1	2		1.347000		0.888800	2.04000
Anxiety and depression combined --- Yes:No	1	2		0.527900	0.17940	0.176300	0.87950
Hazard Ratio	1	2		1.695000		1.193000	2.41000
Maternal morbidity --- Yes:No	1	2		-0.037990	0.35210	-0.728200	0.65220
Hazard Ratio	1	2		0.962700		0.482800	1.92000

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
MOUD receipt timing	1.08	2	0.5841
Total days supplied MOUD (method 3)	1.88	1	0.1708
Year of delivery	19.54	1	<0.0001
Age at delivery	0.73	1	0.3913
Route of delivery	0.01	1	0.9272
Number of Gestation weeks	3.77	1	0.0521
Combined pain	1.91	1	0.1665
Alcohol or other substance use	1.31	1	0.2521
Benzodiazepine or anticonvulsant use	1.97	1	0.1601
Anxiety and depression combined	8.65	1	0.0033
Maternal morbidity	0.01	1	0.9140
TOTAL	69.00	12	<0.0001

Timing only

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Year of delivery	2016	2018	2	0.35050	0.07832	0.197000	0.5040
Hazard Ratio	2016	2018	2	1.42000		1.218000	1.6550
Age at delivery	27	31	4	-0.06796	0.07223	-0.209500	0.0736
Hazard Ratio	27	31	4	0.93430		0.811000	1.0760
Number of Gestation weeks	39	37	-2	0.12390	0.06132	0.003695	0.2441
Hazard Ratio	39	37	-2	1.13200		1.004000	1.2760
MOUD receipt timing --- Only pre:Both pre and post	3	1		0.24200	0.23080	-0.210400	0.6943
Hazard Ratio	3	1		1.27400		0.810300	2.0020
MOUD receipt timing --- Only post:Both pre and post	3	2		0.57760	0.23190	0.123100	1.0320
Hazard Ratio	3	2		1.78200		1.131000	2.8070
Route of delivery --- Cesarean:Vaginal	2	1		-0.02482	0.17700	-0.371700	0.3220
Hazard Ratio	2	1		0.97550		0.689600	1.3800
Combined pain --- No:Yes	2	1		0.25800	0.18610	-0.106800	0.6228
Hazard Ratio	2	1		1.29400		0.898700	1.8640
Alcohol or other substance use --- Yes:No	1	2		0.21430	0.17050	-0.119800	0.5484
Hazard Ratio	1	2		1.23900		0.887100	1.7310
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.29820	0.21190	-0.117200	0.7135
Hazard Ratio	1	2		1.34700		0.889400	2.0410
Anxiety and depression combined --- Yes:No	1	2		0.52590	0.17920	0.174700	0.8770
Hazard Ratio	1	2		1.69200		1.191000	2.4040
Maternal morbidity --- Yes:No	1	2		-0.04240	0.35190	-0.732200	0.6474
Hazard Ratio	1	2		0.95850		0.480900	1.9110

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
MOUD receipt timing	6.55	2	0.0378
Year of delivery	20.01	1	<0.0001
Age at delivery	0.89	1	0.3463
Route of delivery	0.02	1	0.8885
Number of Gestation weeks	4.09	1	0.0432
Combined pain	1.92	1	0.1657
Alcohol or other substance use	1.58	1	0.2086
Benzodiazepine or anticonvulsant use	1.98	1	0.1591
Anxiety and depression combined	8.61	1	0.0033
Maternal morbidity	0.01	1	0.9040
TOTAL	68.51	11	<0.0001

Linear continuous terms (timing + days BUP)

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Total days supplied buprenorphine	1	31	30	-0.151300	0.09334	-0.33420	0.03167
Hazard Ratio	1	31	30	0.859600		0.71590	1.03200
Year of delivery	2014	2018	4	0.728200	0.16020	0.41420	1.04200
Hazard Ratio	2014	2018	4	2.071000		1.51300	2.83600
Age at delivery	25	35	10	-0.142200	0.18150	-0.49800	0.21350
Hazard Ratio	25	35	10	0.867400		0.60770	1.23800
Number of Gestation weeks	37	39	2	-0.124100	0.06054	-0.24280	-0.00545
Hazard Ratio	37	39	2	0.883300		0.78450	0.99460
MOUD receipt timing --- Only pre:Both pre and post	3	1		-0.004516	0.30670	-0.60570	0.59670
Hazard Ratio	3	1		0.995500		0.54570	1.81600
MOUD receipt timing --- Only post:Both pre and post	3	2		0.372200	0.32520	-0.26510	1.01000
Hazard Ratio	3	2		1.451000		0.76710	2.74400
Route of delivery --- Cesarean:Vaginal	2	1		-0.080810	0.18050	-0.43460	0.27300
Hazard Ratio	2	1		0.922400		0.64750	1.31400
Combined pain --- No:Yes	2	1		0.257000	0.18710	-0.10970	0.62380
Hazard Ratio	2	1		1.293000		0.89610	1.86600
Alcohol or other substance use --- Yes:No	1	2		0.271400	0.17210	-0.06591	0.60860
Hazard Ratio	1	2		1.312000		0.93620	1.83800
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.308900	0.21260	-0.10780	0.72560
Hazard Ratio	1	2		1.362000		0.89780	2.06600
Anxiety and depression combined --- Yes:No	1	2		0.532400	0.18040	0.17890	0.88590
Hazard Ratio	1	2		1.703000		1.19600	2.42500
Maternal morbidity --- Yes:No	1	2		-0.040000	0.35290	-0.73160	0.65160
Hazard Ratio	1	2		0.960800		0.48110	1.91900

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
MOUD receipt timing	1.94	2	0.3790
Total days supplied buprenorphine	2.63	1	0.1049
Year of delivery	20.62	1	<0.0001
Age at delivery	0.61	1	0.4330
Route of delivery	0.20	1	0.6546
Number of Gestation weeks	4.21	1	0.0401
Combined pain	1.89	1	0.1696
Alcohol or other substance use	2.49	1	0.1146
Benzodiazepine or anticonvulsant use	2.12	1	0.1458
Anxiety and depression combined	8.70	1	0.0032
Maternal morbidity	0.01	1	0.9096
TOTAL	75.64	12	<0.0001

Timing only BUP

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Year of delivery	2014	2018	4	0.73330	0.15890	0.42180	1.0450
Hazard Ratio	2014	2018	4	2.08200		1.52500	2.8430
Age at delivery	25	35	10	-0.16150	0.18280	-0.51970	0.1967
Hazard Ratio	25	35	10	0.85090		0.59470	1.2170
Number of Gestation weeks	37	39	2	-0.12930	0.06002	-0.24700	-0.0117
Hazard Ratio	37	39	2	0.87870		0.78120	0.9884
MOUD receipt timing --- Only pre:Both pre and post	3	1		0.29380	0.23160	-0.16010	0.7477
Hazard Ratio	3	1		1.34200		0.85200	2.1120
MOUD receipt timing --- Only post:Both pre and post	3	2		0.74020	0.23730	0.27510	1.2050
Hazard Ratio	3	2		2.09600		1.31700	3.3370
Route of delivery --- Cesarean:Vaginal	2	1		-0.09333	0.18000	-0.44620	0.2595
Hazard Ratio	2	1		0.91090		0.64010	1.2960
Combined pain --- No:Yes	2	1		0.25760	0.18730	-0.10950	0.6246
Hazard Ratio	2	1		1.29400		0.89630	1.8670
Alcohol or other substance use --- Yes:No	1	2		0.29550	0.17270	-0.04307	0.6341
Hazard Ratio	1	2		1.34400		0.95780	1.8850
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.31000	0.21260	-0.10680	0.7268
Hazard Ratio	1	2		1.36300		0.89870	2.0680
Anxiety and depression combined --- Yes:No	1	2		0.53030	0.18020	0.17710	0.8834
Hazard Ratio	1	2		1.69900		1.19400	2.4190
Maternal morbidity --- Yes:No	1	2		-0.04663	0.35260	-0.73770	0.6444
Hazard Ratio	1	2		0.95440		0.47820	1.9050

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
MOUD receipt timing	10.20	2	0.0061
Year of delivery	21.27	1	<0.0001
Age at delivery	0.78	1	0.3765
Route of delivery	0.27	1	0.6044
Number of Gestation weeks	4.66	1	0.0310
Combined pain	1.89	1	0.1690
Alcohol or other substance use	2.93	1	0.0870
Benzodiazepine or anticonvulsant use	2.13	1	0.1445
Anxiety and depression combined	8.65	1	0.0033
Maternal morbidity	0.02	1	0.8946
TOTAL	75.18	11	<0.0001

5 Sensitivity analysis 2007-2018

5.1 Descriptive Statistics

• There are 5728 pregnancies in 5049 unique individuals

  	N	Overall
  		(N=7125)
  Year of delivery	7125 (100.00)
  Median (interquartile range)		2015 (2013—2017)
  Range		2007—2018
  Age at delivery	7125 (100.00)
  Median (interquartile range)		27 (24—30)
  Range		17—44
  Number of Gestation weeks	7125 (100.00)
  Median (interquartile range)		39 (37—39)
  Range		21—42
  Race	7125 (100.00)
  American Indian or Alaska Native		18/7125 (0.25)
  Asian or Pacific Islander		9/7125 (0.13)
  Black of African American		159/7125 (2.23)
  Other or Unknown		47/7125 (0.66)
  White		6892/7125 (96.73)
  Hispanic : Not Hispanic	7120 (99.93)	7063/7120 (99.20)
  Race/Ethnicity combined	7125 (100.00)
  Hispanic		57/7125 (0.80)
  Non-Hispanic Asian		8/7125 (0.11)
  Non-Hispanic Black		158/7125 (2.22)
  Non-Hispanic Other		49/7125 (0.69)
  Non-Hispanic White		6853/7125 (96.18)
  Route of delivery : Vaginal	7125 (100.00)	4659/7125 (65.39)
  Number of previous pregnancies	6969 (97.81)
  Median (interquartile range)		2 (1—3)
  Range		0—23
  Final outcome	7125 (100.00)
  Death		28/7125 (0.39)
  Overdose		64/7125 (0.90)
  Loss of enrollment		978/7125 (13.73)
  Censored		6055/7125 (84.98)
  Final outcome (w/o all payer data)	7125 (100.00)
  Death		12/7125 (0.17)
  Overdose		59/7125 (0.83)
  Loss of enrollment		999/7125 (14.02)
  Censored		6055/7125 (84.98)
  Total days supplied MOUD	7125 (100.00)
  Median (interquartile range)		122 (84—132)
  Range		1—132
  Total days supplied MOUD before delivery	7125 (100.00)
  Median (interquartile range)		90 (60—90)
  Range		0—90
  Total days supplied MOUD after delivery	7125 (100.00)
  Median (interquartile range)		42 (14—42)
  Range		0—42
  Total days supplied MOUD (method 2)	7125 (100.00)
  Median (interquartile range)		132 (84—132)
  Range		1—132
  Total days supplied MOUD before delivery (method 2)	7125 (100.00)
  Median (interquartile range)		90 (60—90)
  Range		0—90
  Total days supplied MOUD after delivery (method 2)	7125 (100.00)
  Median (interquartile range)		42 (36—42)
  Range		0—42
  Total days supplied MOUD (method 3)	7125 (100.00)
  Median (interquartile range)		88 (45—110)
  Range		1—132
  Total days supplied MOUD before delivery (method 3)	7125 (100.00)
  Median (interquartile range)		61 (30—76)
  Range		0—90
  Total days supplied MOUD after delivery (method 3)	7125 (100.00)
  Median (interquartile range)		29 (12—40)
  Range		0—42
  Avg dose pre-delivery (mg)	7125 (100.00)
  Median (interquartile range)		14.26 (8.00—16.00)
  Range		0.00—50.00
  Avg dose post-delivery (mg)	7125 (100.00)
  Median (interquartile range)		10.15 (4.00—16.00)
  Range		0.00—380.00
  Avg dose exposure (mg)	7125 (100.00)
  Median (interquartile range)		14.20 (9.98—16.00)
  Range		0.00—380.00
  Total days buprenorphine before delivery (method 3)	6992 (98.13)
  Median (interquartile range)		62.00 (30.00—77.00)
  Range		0.00—90.00
  Total days buprenorphine after delivery (method 3)	6992 (98.13)
  Median (interquartile range)		29.00 (12.00—40.00)
  Range		0.00—42.00
  Total days supplied buprenorphine	6992 (98.13)
  Median (interquartile range)		88.00 (46.00—110.00)
  Range		1.00—132.00
  Avg dose BUP pre-delivery (mg)	6992 (98.13)
  Median (interquartile range)		14.29 (8.00—16.00)
  Range		0.00—40.00
  Avg dose BUP post-delivery (mg)	6992 (98.13)
  Median (interquartile range)		9.60 (3.94—16.00)
  Range		0.00—42.67
  Avg dose BUP exposure (mg)	6992 (98.13)
  Median (interquartile range)		14.17 (9.77—16.00)
  Range		0.00—42.67
  Combined pain : Yes	7125 (100.00)	5769/7125 (80.97)
  Schizophrenia or personality disorder : Yes	7125 (100.00)	502/7125 (7.05)
  Alcohol or other substance use : Yes	7125 (100.00)	3299/7125 (46.30)
  Benzodiazepine or anticonvulsant use : Yes	7125 (100.00)	1100/7125 (15.44)
  Maternal morbidity : Yes	7125 (100.00)	571/7125 (8.01)
  Anxiety and depression combined : Yes	7125 (100.00)	3016/7125 (42.33)
  Back pain : Yes	7125 (100.00)	3033/7125 (42.57)
  Med muscle relaxant use : Yes	7125 (100.00)	353/7125 (4.95)
  Med NSAIDS : Yes	7125 (100.00)	4418/7125 (62.01)
  Bipolar disorder : Yes	7125 (100.00)	691/7125 (9.70)
  Depression : Yes	7125 (100.00)	2609/7125 (36.62)
  Maternal morbidity : Yes	7125 (100.00)	571/7125 (8.01)
  Med benzodiazepine use : Yes	7125 (100.00)	746/7125 (10.47)
  Schizophrenia psychotic disorders : Yes	7125 (100.00)	377/7125 (5.29)
  Tobacco use : Yes	7125 (100.00)	5036/7125 (70.68)
  Dental pain : Yes	7125 (100.00)	270/7125 (3.79)
  Alcohol use disorder : Yes	7125 (100.00)	458/7125 (6.43)
  Other substance use : Yes	7125 (100.00)	3143/7125 (44.11)
  Anxiety : Yes	7125 (100.00)	1153/7125 (16.18)
  Fibromyalgia : Yes	7125 (100.00)	368/7125 (5.16)
  Med anticonvulsant use : Yes	7125 (100.00)	427/7125 (5.99)
  Personality disorder : Yes	7125 (100.00)	208/7125 (2.92)
  CDC SVI overall percentile ranking of all 4 themes	6610 (92.77)
  Median (interquartile range)		0.57 (0.37—0.78)
  Range		0.00—1.00

  N is the number of non-missing value. ¹Kruskal-Wallis. ²Pearson. ³Wilcoxon.

5.1.1 Time to event for overdose and death

deathod18$days.to.event

n	missing	distinct	Info	Mean	pMedian	Gmd	.05	.10	.25	.50	.75	.90	.95
92	0	84	1	182.6	183	107.7	23.4	43.2	111.8	193.5	268.5	295.9	305.8

lowest : 2 7 8 18 19 , highest: 304 308 310 316 319 death18$days.to.event

n	missing	distinct	Info	Mean	pMedian	Gmd	.05	.10	.25	.50	.75	.90	.95
28	0	27	1	163.7	163.5	118.1	24.60	37.10	58.75	174.50	267.75	283.70	293.25

lowest : 2 19 35 38 45 , highest: 279 281 290 295 308 od18$days.to.event

n	missing	distinct	Info	Mean	pMedian	Gmd	.05	.10	.25	.50	.75	.90	.95
64	0	61	1	190.9	195	102.7	29.25	51.80	123.75	213.00	268.50	300.10	309.10

lowest : 7 8 18 27 42 , highest: 302 304 310 316 319

Survival Analysis

5.2 Kaplan Meier Plot

Call: survfit(formula = Surv(days.to.event, outcome.bin) ~ 1, data = moud18)

        n events median 0.95LCL 0.95UCL
[1,] 7125     92     NA      NA      NA

   Min. 1st Qu.  Median    Mean 3rd Qu.    Max. 
    2.0   111.0   184.0   181.1   268.0   323.0 

time	probability
2	0.9998596
7	0.9997193
8	0.9995789
18	0.9994386
19	0.9992982
27	0.9991579
35	0.9990175
38	0.9988772
42	0.9987368
43	0.9985965
45	0.9984561
47	0.9983158
52	0.9980351
61	0.9978947
63	0.9977544
66	0.9976140
69	0.9974737
72	0.9973333
91	0.9971930
97	0.9970526
110	0.9969123
111	0.9967719
112	0.9966316
118	0.9964912
120	0.9963509
125	0.9962105
128	0.9960702
131	0.9959298
138	0.9956491
140	0.9955088
144	0.9953684
147	0.9952281
156	0.9950877
166	0.9949474
169	0.9948070
171	0.9946667
175	0.9945263
177	0.9943860
178	0.9942456
180	0.9941053
181	0.9939649
182	0.9938246
184	0.9936842
188	0.9935439
199	0.9934035
208	0.9932632
213	0.9929825
215	0.9928421
217	0.9925614
220	0.9924211
222	0.9922807
223	0.9921404
228	0.9920000
229	0.9918596
235	0.9917193
239	0.9915789
240	0.9912982
244	0.9911579
246	0.9910175
258	0.9908772
261	0.9907368
265	0.9905965
267	0.9904561
268	0.9903158
270	0.9900351
271	0.9898947
272	0.9897544
274	0.9896140
275	0.9894737
279	0.9893333
281	0.9891930
287	0.9890526
289	0.9889123
290	0.9887719
295	0.9884912
296	0.9883509
298	0.9882105
301	0.9880702
302	0.9879298
304	0.9877895
308	0.9876491
310	0.9873684
316	0.9872281
319	0.9870877
323	0.9870877

Multivariable Cox PH model

5.2.1 Linear continuous terms

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Year of delivery	2016	2018	2	0.28280	0.11690	0.05362	0.51190
Hazard Ratio	2016	2018	2	1.32700		1.05500	1.66900
Total days supplied MOUD (method 3)	1	31	30	-0.22850	0.07834	-0.38200	-0.07497
Hazard Ratio	1	31	30	0.79570		0.68250	0.92780
Age at delivery	27	31	4	-0.03437	0.09495	-0.22050	0.15170
Hazard Ratio	27	31	4	0.96620		0.80210	1.16400
Number of Gestation weeks	39	37	-2	0.15990	0.07556	0.01176	0.30800
Hazard Ratio	39	37	-2	1.17300		1.01200	1.36100
Route of delivery --- Cesarean:Vaginal	2	1		0.18580	0.21990	-0.24520	0.61670
Hazard Ratio	2	1		1.20400		0.78260	1.85300
Combined pain --- No:Yes	2	1		0.26780	0.25060	-0.22340	0.75900
Hazard Ratio	2	1		1.30700		0.79980	2.13600
Alcohol or other substance use --- Yes:No	1	2		-0.11430	0.21490	-0.53560	0.30690
Hazard Ratio	1	2		0.89200		0.58530	1.35900
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.25130	0.26480	-0.26770	0.77030
Hazard Ratio	1	2		1.28600		0.76510	2.16000
Anxiety and depression combined --- Yes:No	1	2		0.56230	0.22270	0.12590	0.99870
Hazard Ratio	1	2		1.75500		1.13400	2.71500
Maternal morbidity --- Yes:No	1	2		-0.12120	0.42510	-0.95440	0.71210
Hazard Ratio	1	2		0.88590		0.38510	2.03800

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
Year of delivery	5.84	1	0.0157
Total days supplied MOUD (method 3)	8.51	1	0.0035
Age at delivery	0.13	1	0.7172
Route of delivery	0.71	1	0.3983
Number of Gestation weeks	4.48	1	0.0342
Combined pain	1.14	1	0.2853
Alcohol or other substance use	0.28	1	0.5945
Benzodiazepine or anticonvulsant use	0.90	1	0.3421
Anxiety and depression combined	6.37	1	0.0116
Maternal morbidity	0.08	1	0.7756
TOTAL	45.08	10	<0.0001

5.2.2 Univariable HR

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Total days supplied MOUD (method 3)	1	31	30	-0.2480	0.07827	-0.4015	-0.09463
Hazard Ratio	1	31	30	0.7803		0.6693	0.90970

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
Total days supplied MOUD (method 3)	10.04	1	0.0015
TOTAL	10.04	1	0.0015

6 Sensitivity analysis shift-forward

	N	Overall
		(N=9048)
Total days supplied MOUD (method 3)	9048 (100.00)
Median (interquartile range)		88 (43—111)
Range		1—132
MOUD days exposure shifted approach	9048 (100.00)
Median (interquartile range)		111 (65—126)
Range		1—132

N is the number of non-missing value. ¹Kruskal-Wallis. ²Pearson. ³Wilcoxon.

6.1 Survival Analysis

Multivariable Cox PH model

Linear continuous terms

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Year of delivery	2016	2018	2	0.35000	0.07915	0.194800	0.50510
Hazard Ratio	2016	2018	2	1.41900		1.215000	1.65700
MOUD days exposure shifted approach	1	31	30	-0.14610	0.05798	-0.259700	-0.03245
Hazard Ratio	1	31	30	0.86410		0.771200	0.96810
Age at delivery	27	31	4	-0.06104	0.07196	-0.202100	0.08000
Hazard Ratio	27	31	4	0.94080		0.817000	1.08300
Number of Gestation weeks	39	37	-2	0.12370	0.06192	0.002358	0.24510
Hazard Ratio	39	37	-2	1.13200		1.002000	1.27800
Route of delivery --- Cesarean:Vaginal	2	1		-0.01795	0.17740	-0.365700	0.32980
Hazard Ratio	2	1		0.98220		0.693700	1.39100
Combined pain --- No:Yes	2	1		0.25950	0.18610	-0.105200	0.62420
Hazard Ratio	2	1		1.29600		0.900200	1.86700
Alcohol or other substance use --- Yes:No	1	2		0.19700	0.17080	-0.137700	0.53170
Hazard Ratio	1	2		1.21800		0.871400	1.70200
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.29990	0.21200	-0.115600	0.71530
Hazard Ratio	1	2		1.35000		0.890800	2.04500
Anxiety and depression combined --- Yes:No	1	2		0.53120	0.18010	0.178200	0.88420
Hazard Ratio	1	2		1.70100		1.195000	2.42100
Maternal morbidity --- Yes:No	1	2		-0.03141	0.35210	-0.721400	0.65860
Hazard Ratio	1	2		0.96910		0.486100	1.93200

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
Year of delivery	19.52	1	<0.0001
MOUD days exposure shifted approach	6.35	1	0.0117
Age at delivery	0.72	1	0.3958
Route of delivery	0.01	1	0.9195
Number of Gestation weeks	4.00	1	0.0455
Combined pain	1.95	1	0.1630
Alcohol or other substance use	1.33	1	0.2486
Benzodiazepine or anticonvulsant use	2.00	1	0.1568
Anxiety and depression combined	8.69	1	0.0032
Maternal morbidity	0.01	1	0.9289
TOTAL	65.88	10	<0.0001

6.1.1 Univariable HR

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
MOUD days exposure shifted approach	1	31	30	-0.1698	0.05805	-0.2836	-0.05601
Hazard Ratio	1	31	30	0.8438		0.7531	0.94550

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
MOUD days exposure shifted approach	8.55	1	0.0035
TOTAL	8.55	1	0.0035